Pharmacological characterization of AZD5069, a slowly reversible CXC chemokine receptor 2 antagonist.

In normal physiologic responses to injury and infection, inflammatory cells enter tissue and sites of inflammation through a chemotactic process regulated by several families of proteins, including inflammatory chemokines, a family of small inducible cytokines. In neutrophils, chemokines chemokine (CXC motif) ligand 1 (CXCL1) and CXCL8 are potent chemoattractants and activate G protein-coupled receptors CXC chemokine receptor 1 (CXCR1) and CXCR2. Several small-molecule antagonists of CXCR2 have been developed to inhibit the inflammatory responses mediated by this receptor.

Unprecedented steric deformation of ortho-carborane.

The reduction and subsequent oxidation of meta-carboranes containing bulky groups attached to the cage C atoms affords sterically-crowded ortho-carboranes with unprecedentedly long C-C connectivities.